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MicroPubl Biol,
2019]
Infections by helminths are one of the major health problems in developing countries. Fast adaptation of parasitic organisms has conferred resistance to drug therapies used for decades (Burns et al., 2015), causing a threat to control worm parasites and generating an urgent need for new emergent molecules with therapeutic potential, in particular for nematodes. The nematode Caenorhabditis elegans is phylogenetically-related to parasitic species of helminths in which high throughput assays are challenging; thus, this species is an excellent model to study and evaluate novel anthelmintic drugs (Gilleard, 2004; Yoon et al., 2006). One interesting molecular target for drug development are the GABA receptors of parasitic helminths which are evolutionarily preserved in invertebrates and vertebrates and are present in C. elegans (Castillo et al., 1967; del Castillo et al., 1964; Jorgensen, 2005). GABA receptors from C. elegans are ionotropic channels that belong to the Cys-loop superfamily of ligand gated ion channels widely spread in multiple species, including humans (Olsen and Sieghart, 2008).
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MicroPubl Biol,
2020]
Triclosan (TCS) is a chlorinated, phenolic antimicrobial (Fig. 1A) widely used in personal care products, such as antiseptics and disinfectants, and as an additive in cosmetics, household cleaners, plastics, paints, and textiles, among others (Alfhili and Lee 2019). Despite restricted commercial use in the USA, TCS is still detected at very high rate in human samples (Weatherly and Gosse 2017), possibly because of increased use in building materials, or older polypropylene copolymers (PPCs). TCS has raised concerns regarding its health risks and environmental impact (Alfhili et al.. 2019; Weatherly and Gosse 2017; Yueh and Tukey 2016). In terms of risk assessment, C. elegans has been a successful animal model for toxicological profiling as it allows for monitoring of vital physiological endpoints such as body length, locomotion, development, brood size, and survival (Meyer and Williams 2014). We have previously shown that TCS disrupts SKN-1/Nrf2-mediated oxidative stress response in C. elegans larvae (Yoon et al.. 2017). Here, we examine the hatching rate of C. elegans wild-type (N2) embryos in response to acute TCS exposure (see Methods). As shown in Fig. 1B-1D, TCS caused pronounced shrinkage of the inner cell mass of embryos in a dose-dependent fashion. As the inner cell mass shrinks, we speculate that TCS may disturb the osmotic regulation of the developing embryo. Of note, we have recently reported that non-ionic surfactants antagonize the toxicity of phenolic endocrine-disrupting chemicals in C. elegans larvae (Alfhili et al.. 2018). Likewise, the non-ionic surfactant polysorbate 20 (also known as Tween 20; Tw20), significantly ameliorated TCS-induced mortality and restored hatching to physiological rates (Fig. 1B and 1E). Since hydrophobic substances may be emulsified in micelles formed by non-ionic surfactants, we suggest that Tw20 may inhibit TCS-induced embryonic mortality by micellar solubilization.